Week 5 Flashcards
List the 10 features of Parkinson’s Disease?
- Tremor at rest
- Rigidity: cogwheel, limbs>axial
- Bradykinesia
- Asymmetry
- Loss righting reflex
- 30% cognitive decline
- Hypomimia (lack facial expression)
- Glabellar tap
- Quiet Speech
- Micrographia
What neurotransmitters inhibit & excite the basal ganglia?
- INHIBIT: GABA
- EXCITE: Glutamate
What happens in the substantial nigra dopaminergic part of the corticospinal pathway?
- Turns up direct pathway
- Turns down the indirect pathway
- Increases VA/VL drive to cortex
- MORE MOTOR ACTIVITY
Describe the direct corticospinal pathway?
- Increases excitatory thalamic input to cortex
- TURNS UP MOTOR ACTIVITY
Describe the indirect corticospinal pathway?
- Decreases excitatory thalamic input to cortex
- TURNS DOWN MOTOR ACTIVITY
What happens in the Striatal interneuron cholingeric part of the corticospinal pathway?
- Turns down direct pathway
- Turns up indirect pathway
- Decreases VA/VL drive to cortex
- LESS MOTOR ACTIVITY
What happens to the corticospinal pathway in Parkinson’s disease?
- Substantia nigra dopamine cells lost, therefore indirect pathway increases
- Dopamine inhibition lost (disinhibition)
- ACh excitation unopposed
- LESS MOTOR ACTIVITY
What 9 factors can lead to Neurodegeneration?
- Toxins
- Protein handling disorders
- Lack of growth factors
- Oxidative stress
- Excitotoxicity
- Ionic disequilibrium
- Mitochondrial dysfunction
- Activation of cell death pathways
- Immune attack
What is the main strategy in drug treatment of Parkinson’s disease?
Counteract deficiency of dopamine in basal ganglia
What are the 5 different drug treatments for Parkinson’s disease?
- Levopoda (1st line)
- Dopamine agonists
- Monoamine oxidase B (MAO-B) inhibitors
- Amantadine
- Muscarinic ACh antagonists
What is Levodopa used in combination with to treat Parkinson’s disease?
Dopa decarboxylase inhibitor (carbidopa or benserazide)
What do 80% of patients on Levodopa for Parkinson’s show?
Initial improvement in rigidity & hypokinesia
What does L-dopa show no evidence of?
That it slows or accelerates neurodegeneration
What are the potential side effects of Levodopa?
- Involuntary writhing movements (dyskinesia) within 2 years (face & limbs mainly), at peak therapeutic effect
- Rapid fluctuations in clinical state
- Hypokinesia & rigidity may suddenly worsen & improve again
Give examples of Dopamine agonists?
- Pramipexole & Roprinole (D2/3 selective receptor agonists)
- Bromocriptine, Cabergoline & Pergolide (oral D1 & D2 receptors)
- Rotigotine
- Apomorphine
What 2 dopamine agonists are better tolerated?
- Pramipexole
2. Roprinole
What is the limiting side effect of Bromocriptine, Carbergoline & Pergolide dopamine agonists?
Fibrotic reactions
How is Rotigotine dopamine agonist administered?
Transdermal patch
How is Apomorphine dopamine agonist administered?
Injection, sometimes to control off effect of Levodopa
Describe the characteristics of Dopamine dysregulation syndrome?
- Sudden onset sleep
- Impulse control disorders (gambling, binge eating)
- Hypotension
- Neuroleptic malignant syndrome if stopped abruptly
Give 2 examples of MAO-inhibitors for Parkinson’s disease?
- Selegiline
2. Rasagiline
Describe Selegiline (MAO-inhibitor)?
Selective MAO-B which lacks unwanted peripheral effects of non- selective MAO inhibitors
What does inhibition of MAO-B do?
Protects dopamine from extraneuronal degradation
What does a combination of MAO-inhibitors & Levodopa provide?
More effective in relieving symptoms & prolonging life
Describe Rasagiline (MAO-inhibitor)?
Alternative & may retard disease progression
Describe the use of Amantadine in Parkinson’s disease?
- Antiviral drug
- Increased dopamine release
- Less effective than levodopa/bromocriptine & action declines with time
How do acetylocholine antagonists work for treatment in Parkinson’s disease?
Exert inhibitory effect on dopaminergic nerves, suppression then compensates for a lack of dopamine
Give 3 examples of Acetylcholine antagonists used in treatment for Parkinson’s disease?
- Benzhexol
- Orphenadrine
- Procyclidine
What is used in severe cases of Parkinson’s disease?
- Electrical stimulation of subthalamic or Gpi nuclei by inserted electrodes (DBS)
- Can improve motor dysfunction
What does combining Levodopa with a dopa decarboxylase inhibitor provide?
Lowers the dose needed & reduces peripheral system effects
What’s a disorder that can occur from an unstable trinucleotide repeat in the exonic coding region?
Huntington’s Disease
polyglutamine in coding region
What’s a disorder that can occur from an unstable trinucleotide repeat in the 5 prime untranslated region?
Fragile X syndrome
What is a disorder that can occur from an unstable trinucleotide repeat in the intronic region?
Fredreich’s Ataxia
What is a disorder that can occur from an unstable trinucleotide repeat in the 3 prime untranslated region?
Myotonic Dystrophy
Describe the characteristics of Huntington’s disease?
- Autosomal dominant
- Begins in midlife
- Chorea, dystonia, behavioural & psychiatric changes, gradual loss of cognition
What structures in the brain are affected in Huntington’s disease?
- Striatum most severely affected
- Atrophy of caudate nucleus & putamen
What does CAG code for?
Glutamine
Why is the insertion of extra glutamine residues in Huntingtin’s protein harmful?
- Protein misfolds
- Aggregates
- Inclusion bodies
What are the 2 ethical questions surrounding Huntington’s disease?
- Does an asymptomatic at-risk individual have a duty to undergo testing & learn result before reproducing?
- Is it ethical to allow asymptomatic children from families with HD to be tested?
Describe the characteristics of Fragile X syndrome?
- Leading cause of inherited mental impairment
- Single gene disorder on X chromosome
- Males & females all ages & ethnic groups
Where is the “fragile” site located for Fragile X syndrome?
Chromosome Xq27.3
What are the signs & symptoms of Fragile X syndrome?
- Long face (prominent forehead & jaw)
- Mitral valve prolapse
- Mental impairment
- Attention deficit / hyperactivity disorder
- Autistic-like behaviour
What protein is associated with Fragile X syndrome?
FMR1
What does the expansion of DNA in Fragile X syndrome result in?
Transcriptional silencing
What is the purpose of FMR1 protein?
Fragile X syndrome
- Highly expressed in neurons
- Regulates mRNA translation in dendrites
Describe the DNA expansion mechanism?
Triplet repeats in human disease can adopt hairpin conformations in vitro at physiological salt levels & temperatures
What is the definition of Genetic Anticipation?
Genetic disorder is passed onto next generation, symptoms become apparent earlier with each generation & increase in severity
What 3 things does genetic anticipation help with clinically?
- Diagnosis
- Genetic counselling
- Treatment
What are the 2 different types of Alzheimers disease?
- Early onset
2. Sporadic
Describe the characteristics of Early onset Alzheimer’s disease?
- Autosomal dominant
- ~5% of all Alzheimer’s
- Down’s Syndrome high risk
What is Amyloid precursor protein (APP) normally cleaved by?
Alpha-secretase & cut into smaller fragments
What happens during Amyloid precursor protein (APP) mutation?
- Increase beta-secretase cleavage of APP
- Leads to excess amyloid accumulation
- Beta-amyloid gives rise to plaques
- Synaptic loss & neuronal death leading to Alzheimer’s
What do mutations in Presenilin 1 & 2 cause?
associated with Alzheimer’s disease
Affect the activity of the gamma-secretase enzyme complex
What gene mutation is involved in sporadic Alzheimer’s disease?
Apolipoprotein E (APOE)
What are the 3 alleles for APOE gene?
e2, e3 & e4
differ by single amino acid
What risk of developing Alzheimer’s disease does heterozygotes for e4 (APOE allele) have?
3 fold risk
What risk of developing Alzheimer’s disease does homozygotes for e4 (APOE allele) have?
15 fold risk
What are the functions of the APOE gene (Apolipoprotein E)?
- Cholesterol transport
- Clears amyloid beta
What can the breakdown of APOE e4 allele cause?
Generate toxic products
What 3 other gene replications are associated with Alzheimer’s disease?
- Clusterin
- PICLAM
- CR1
Describe neurofibrillary tangles?
- Insoluble twisted fibers found inside the brain’s cells
- Consist primarily of tau protein, which stabilises microtubule
Describe neurofibrillary tangles in Alzheimer’s disease?
Tau protein is phosphorylated & the microtubule structures collapse due to depolymerisation
When would you see neurofibrillary tangles but NO plaques in Alzheimer’s disease?
Fronto-temporal dementia with Parkinsonism
How can you therapeutically target neurofibrillary tangles & amyloid plaques in Alzheimer’s?
- Secretase inhibitors
- Prevent phosphorylation of Tau
- Aggregation inhibitors (Tau & amyloid beta)
- Statins
- Immunization
What 3 different prion diseases are grouped as “Transmissible Spongiform encephalopathy”?
- Creutzfeld-Jakob Disease (CJD)
- Fatal familial insomnia
- Kuru
Describe the characteristics of Prion diseases?
- Inherited (10-15%)
- Sporadic (85%)
- Acquired (normally rare)
What are Prion diseases also known as?
Transmissible Spongiform encephalopathy
Describe a Prion?
- Proteinaceous/Infectious
- Progressive neurodegenerative
- No genetic material
- Exist in animals & humans
What is the normal & abnormal infectious Prion’s known as?
- NORMAL: PrPc
- ABNORMAL, INFECTIOUS: PrPsc
What are the 3 normal functions of the PRPN Prion?
- GPI-anchor
- Glycosylated
- Synaptic membranes of neurons
What are the 3 therapies for Prion disease?
- Stabilising PrPC conformation
- Clearance of PrPSC
- Vaccination against PrPSC
What causes an abnormal red reflex?
Anything obstructing path of light from front to back of the eye:
- Corneal Scar
- Cataract
- Vitreous Haemorrhage
- Retinoblastoma
What was the Knudson “2 hit” hypothesis?
Noticed there was patients with family history of retinoblastoma (familial form) & those without (sporadic)
Describe the Familial form of retinoblastoma?
Present earlier in childhood & often had bilateral multi-focal disease
Describe the Sporadic form of retinoblastoma?
Without family history presented later & only had
a single eye involved
What is a tumour suppressor gene (TSG)?
Anti-oncogene
What 3 things do you focus on when examining the optic nerve during ophthalmoscope?
- Margin
- Colour
- Cup
What does a big cup to optic disc ratio mean?
Potential Glaucoma
What are the 4 different types of abnormal optic discs?
- Swollen
- New vessels (diabetes)
- Cupped (glaucoma)
- Pale (optic atrophy)
Describe the 3 different causes of a swollen optic disc?
- Pseudo swelling- small disc, drusen (white accumulations)
- Genuine swelling
- Raised ICP- space occupying lesion, idiopathic intracranial hypertension, hydrocephalus
What is Retinopathy of Prematurity (ROP)?
Blinding neovascular retinal condition driven by hormones including vascular endothelial growth factor (VEGF)
What is a binocular indirect ophthalmoscope?
Wide field manual retinal examination for diabetes & retinopathy of prematurity
What is an Arclight?
Direct ophthalmoscope, Otoscope & Loupe
What are the 6 extra-ocular muscles & their innervation?
- Medial (CN III) & Lateral (CN VI) recti
- Superior & inferior recti (CN III)
- Superior (CN IV) & inferior (CN III) obliques
Describe the clinical presentations of a 3rd (oculomotor) cranial nerve palsy?
- Oblique diplopia
- Eye is ‘down & out’
- Diplopia every where
- Pupil dilated & ptosis
- Can be associated with aneurysm: needs urgent brain imaging & angiogram
Describe the clinical presentations of a 4th (trochlear) cranial nerve palsy?
- Oblique diplopia
- Head tilt
- Worse away from side of the
palsy if unilateral - Common after
head injury - Bilateral: might be congenital
Describe the clinical presentations of a 6th (abducens) cranial nerve palsy?
- Horizontal diplopia
- Worse far distance
- Worse towards side of the palsy if unilateral
- Bilateral: raised intracranial pressure might be present
Describe Age related Macular Degeneration (AMD)?
- Most common cause of blindness >65 years in high- income countries
- Types: wet & dry
What are the symptoms of age related macular degeneration (AMD)?
- Progressive reduction in
visual acuity - Metamorphopsia may suggest wet type
What are the potential treatments for wet & dry Age related macular degeneration (AMD)?
- DRY: rehabilitation
- WET: anti-VEGF injections
When/Where is diabetic retinopathy most common?
Main cause of blindness in working age ‘western’ countries
How does diabetic retinopathy cause blindness?
- Growth of new vessels, vitreous haemorrhage, tractional retinal detachment & rubeotic glaucoma
- Leakage of fluid from damaged vessels, Macular oedema with loss of central visual acuity
Describe the pathological steps of diabetic eye disease?
Chronic hyperglycaemia –> Glycosylation of protein/BM –> Loss of pericytes –> Reduced O2 transport –> VEGF produced –> Neo-vascularisation & leakage
What causes retinal detachment in diabetic retinopathy?
Scaring leading to traction between vitreous & retina
What leads to robotic glaucoma?
New vessel growth on iris
What are the 3 classifications of diabetic retinopathy?
- No retinopathy (screen)
- Non-proliferative retinopathy: Mild, Moderate, Severe (screen mild & refer mod-severe)
- Proliferative retinopathy (treat)
List the signs of non-proliferative diabetic retinopathy?
- Microaneurysms
- Dot & blot haemorrhages
- Hard exudates
- Cotton wool spots
- Abnormalities of venous calibre
- Intra-retinal microvascular abnormalities (IRMA)
What are the 4 classifications of Maculopathy?
- No maculopathy (screen)
- Observable (screen)
- Referable (refer)
- Clinically significant (treat)
What are the 6 potential treatments for Maculopathy?
- Stop smoking, weight, exercise
- Glycaemic control
- Blood pressure control
- Dyslipidaemia control
- Support renal function- ACE inhibitors
- Laser, anti-VEGF injections & surgery
Where do 80% of people with diabetes live?
In low & middle income countries
What is the main cause of blindness in “Western” countries?
Age related macular degeneration (AMD)
What is the main cause of blindness in “low income” countries?
Cataract
What are the 5 most common types of Dementia?
- Alzheimer’s
- Vascular
- Mixed
- Fronto-temporal
- Dementia with Lewy bodies
What is Dementia according to NICE guidelines 42?
Dementia is a generic term for clinical syndrome & progressive
How does Dementia affect the person (5)?
- Day to day memory
- Mood
- Language/
communication problems - Visuospatial skills
- Orientation
- Concentrating, planning, organising
List the signs & symptoms of Early “mild” stage Alzheimer’s?
- Forgetful
- Lose interest
- Mislaying items
- Poor judgement, hard to make plans/decisions
- Confusion
- Slower cognitive capacity
- Judging distance
List the signs & symptoms of Middle “moderate” stage Alzheimer’s?
- Fail to recognise people
- Time/place/events/getting lost
- Need help with personal care
- Difficulty in daily activities
- Safety
- Behavioural changes
List the signs & symptoms of Late stage Alzheimer’s?
- Unaware of time/place
- Confusion/comprehension
- Not recognise familiar faces
- Need assistance in eating
- Increased need in self case
- Incontinence
- Mobility problems
What is the role of the Caregiver in early stage Dementia?
- Emotional support
- Prompt & remind person about events, tasks to maintain involvement & independence
- Assistance with instrumental activities (personal finances, shopping)
What is the role of the Caregiver in middle stage Dementia?
- Communication strategies
- Help with personal care
- Help with activities of daily living (food preparation, dressing appropriately)
- Respond & manage behavioural disturbance & inappropriate behaviour
What is the role of the Caregiver in late stage Dementia?
- Care, support & supervision 24/7
- Assistance with eating & drinking
- Full physical care (bathing, toileting,
dressing, mobilizing) - Manage behavioural problems
What are the consequences of caregiving?
- Depression/anxiety
- Lower quality of life/wellbeing
- Worse health outcomes
- Sleep problems
- Socially isolated
- Role strain
- Family conflict
- Financial strain
- Sense of loss/grief
- Guilt/ resentment/ anger
What are 2 false beliefs of Dementia?
- Normal part of ageing
2. Nothing can be done
What are 4 sources of support for people with Dementia?
- Social services department of local authority/council
- Community psychiatric nurse
- Physiotherapy (mobility)
- Occupational therapy
How does Occupational therapy help with Dementia?
- Reminiscing & making life story book
- Recommending suitable exercise/
changes around home - Improve home safety
- Info accessing other support
- Advising carers
Give 4 examples of Motorneurone diseases?
- Amyotrophic lateral sclerosis (UMN & LMN)
- Progressive muscular atrophy (LMN)
- Primary lateral sclerosis (UMN)
- Spinal muscular atrophy
What is the average life expectancy of motorneurone disease?
~3 years
What are the 3 genes associated with Alzheimer’s disease?
- Amyloid precursor protein (chromosome 21) trisomy, mutations, duplications
- Presenilin-1 (chromosome 14) mutations
- Presenilin-2 (chromosome 2) mutations
What are 4 genes associated with ALS?
- Superoxide Dismutase 1
- TAR DNA Binding
Protein (TDP-43) - Fused in Sarcoma (FUS)
- C9orf72 (most common)
What drug can be used for Amyotrophic lateral sclerosis (ALS)/ Motor neurone disease (MND)?
Riluzole
take for 18months, live a further 3months
What are the 5 mechanisms of Riluzole action?
- Block TTX Na channels
- Reduces Glutamate release (Calcium block)
- Increases astrocyte glutamate uptake
- Enhances GABA activity
- Enhances BDNF action
How common is Alzheimer’s disease?
70% of all dementia
Are males or females more likely to develop Alzheimer’s disease?
Females
What do hyperphosphorylated tau in Neurofibrillary tangles form?
Paired helical filaments
What are amyloid plaques in Alzheimer’s largely composed of?
Aβ peptides, either
diffuse/neuritic (surrounded by dystrophic neurites)
What are the neurochemical changes in Alzheimer’s disease?
- Loss of ACh, from neuronal loss from nucleus basalis of Meynert
- GABA loss from cortex due to neuronal loss
- Serotonin (5HT) input from dorsal raphe nuclei reduced
- Noradrenaline input from locus ceruleus reduced
What is the most common cognitive measurement instrument used for clinical trials in Alzheimer’s disease?
ADAS-cog
What are the possible explanations for failed clinical trials in neurodegenerative disorders?
- Drug doesn’t work
- Population not changing, won’t see effect
- Measurement instruments inadequate
- Higher level disability beyond potential help
- Differential effects at different levels
What 3 points does the Royal Collage of Physicians report on Future Hospital Commission state?
- People’s needs are often complex
- Care, treatment & support services by a range of professionals must work in collaboration
- Most vulnerable patients (old, frail) are failed by system & seemingly unwilling to meet their needs
What 2 points does the Royal Collage of Physicians report on Education, training & deployment of doctors?
- Need knowledge of continuing care for increasing no. of patients with multiple, complex conditions
- Importance of acute & general internal medicine
What is the doctor’s role frail older people?
- Consider all needs & issues
- “Whole person” approach even in speciality medicine
- Don’t only see the disease
What is the doctor’s aim for frail older patients?
Improve wellbeing & help regain function & a similar degree of independence they had before current acute episode
What are death rates from particular conditions affected by?
- Incidence (new cases) of a condition
2. Survival rates from that condition
Describe the age-specific mortality rates for coronary heart disease?
Incidence of new cases falling & survival rates increasing= mortality rates falling
What is the trend for health service use?
Health & mortality rates are improving but health services under more pressure
Describe the prevalence of chronic disease/long term conditions?
Prevalence of many conditions rises with age (higher incidence due to ageing population & longer survival due to advanced care & treatment)
With an ageing population, what is important in the healthcare system?
Staff factor dementia into services, care & treatment plans in old age & understand basics of dementia care & needs of dementia patients
What does WHO say about the implications of global ageing?
- Life-long promotion & prevention can prevent/delay onset of non-communicable & chronic diseases
- Detected & treated early to minimise consequences
- Advanced disease need long term care & support
- Comprehensive primary care
What point does the report on “Making our health & care systems fit for an ageing population” state?
Never assume that ‘it’s just their age’, or the only thing that counts is compassionate care
How can doctors work with others to meet the needs of older individuals?
Assessment/setting up “packages of care” with different agencies in a timely fashion (social work, home care & voluntary services)
What is the bedrock of the pyramid for self care & management in long-term conditions?
Community networks & support
What is the aim of the pyramid for self care & management in long-term conditions?
Provide/support care at appropriate level
Describe the rationale behind the new model of acute management- Hospital at Home?
- Family & carers still involved
- No disorientation from hospital environment
- Quicker return to function
- Links to community services & social care
- Avoids hospital bed use unless it is absolutely needed
What are the challenges behind the new model of acute management- Hospital at Home?
Needs good clinical & care processes to provide safe hospital care in the home
How can doctors help the process of dying?
- Palliative Care Approach
- Open approach to Death, Dying & Bereavement across society
What does the Palliative care approach address?
- Physical, psychological, social & spiritual needs of patient & families
- Integral to all clinical practice, whatever illness or stage
What is Palliative care comprised of?
- Quality of life
- Whole person approach
- Account of person’s & carers views
- Respects autonomy & choice
- Open & sensitive communication
What are the 2 common misconceptions about Palliative care?
- Not just the province of specialists
2. Not only relevant at the end of life, arise throughout an illness trajectory
Who gets involved when there are complex problems to deal with?
Specialist Palliative care services & other specialist services
What fraction of diagnosed dementia patients live in a care home?
1/3
What are the 4 key points about dementia?
- A syndrome, not specific diagnosis
- Only definitive diagnostic test is pathology, post-mortem
- No reliable biomarker
- Nothing to alter course of disease
What are the functions of the brains frontal lobes?
Sequencing & fluency
How can we assess cognition in the frontal lobes?
- Luria hand sequencing tasks
2. Verbal fluency 1min words starting with F,A,S or list animals
What are the functions of the brains temporal lobes?
Memory & Speech (left hemisphere)
How can we assess cognition in the temporal lobes?
- Address test
- Object recall
- Serial 7 (start at 100 and -7)
What are the functions of the brains parietal lobes?
Spatial awareness (right), language (left)
How can we assess cognition in the parietal lobes?
- Draw clock face
- Naming objects
- Drawing cube, interlocking infinity signs
- Agnosia
Describe the Minimental test (MMSE)?
- Max score 30
- Insensitive, lack responsiveness
- Have to be pretty demented
Describe the Addenbrookes Cognitive Examination (ACE)?
- 15 to 20mins
- Multi-domain
- 13 validated translations
- Score out of 100
Describe the ACE-R Psychometrics test?
- Good reliability
- Score of 82
What are the features of the ACEmobile app?
- Auto-scoring
- Auto-reporting
- Standardised administration
- Cloud data backup
When do pathological changes of the brain happen in relation to Dementia symptoms?
Commence well in advance (15-30yrs) of dementia symptoms
What is Mild cognitive impairment (MCI)?
Subjective memory impairment & cognitive impairment not meeting dementia diagnostic criteria
How does early diagnosis of Dementia affect the outcome of patient?
- Slower cognitive decline & decrease mortality
- Better quality of life, dignity & rights
- Delayed admission to institutional care
- Improvement in challenging behaviour & opportunities for social participation
What are the 2 broad groups of early diagnostic investigations for Alzheimer’s disease?
- Neuroimaging (CT, MRI, SPECT, FDG-PET, Amyloid)
2. Biomarkers of alzheimer’s disease
How does Perfusion SPECT imagining detect Alzheimer’s disease (AD)?
- Image variations in regional cerebral blood flow which display charactersitic abnormalities in early AD
How does FDG-PET imagining detect Alzheimer’s disease?
Uptake of FDG proportional to cerebral glucose metabolism, so indicator of cerebral metabolism
What are the 3 main CSF markers investigated for diagnosis & management of Alzheimer’s disease?
- Amyloid- β42 (Aβ42)
- Total tau (t-tau)
- Phosphorylated tau (p-tau)
Can CSF markers reliably predict development of Alzheimer’s disease in healthy individuals?
NO
Describe Neuropsychiatric symptoms?
- Affects 90% patients
- Present throughout disease course
- May remit but highly recurrent
- Likely most problematic aspect for carers
- Strongly associated with nursing home placement
What are the 6 steps to Dementia assessment & Diagnosis bundle (DAB)?
- Patient interview
- Cognitive examination
- Informant interview
- Investigations
- Specialist assessments
- Diagnostic confirmation
Why is the patient cognitive assessment in dementia assessment & diagnosis bundle essential?
Patients may deny any issues relating to their memory & present with good social façade masking cognitive challenges
Describe the informant interview in dementia assessment & diagnosis bundle?
- Relative/close individual to describe any changes noticed in the memory abilities/functioning of patient
- Structured informant questionnaire may be used (IQCODE, p48 SIGN86)
What 3 investigations would you do for the dementia assessment & diagnosis bundle?
- Haematological (FBC, B12, folate)
- Biochemical (U&E, Glucose/ HbA1c, LFT, Ca, PO4, Cholesterol, TSH)
- Radiological (CT/ MRI brain within previous 12months)
Describe the 5 different types of specialist assessments for the dementia assessment & diagnosis bundle?
- Psychometric (Clinical Psychologist)
- Activities of Daily Living (Occupational Therapist)
- Speech & Language Therapist
- Neurologist
- Medical co-morbidity or fraility syndrome (Geriatrician)
Describe how you can confirm a diagnosis of dementia?
Reference to ICD/ Diagnostic & Statistical Manual of Mental Disorders (DSM) diagnostic schedules
Describe the chain of lymphatic system of the body?
Blood capillaries –> Interstitial fluid (+ lymphocytes/APC) –> Lymph capillaries –> Lymph nodes –> Lymph vessels –> Veins
What happens to the flow once in the lymphatic system?
Its vectorial
What does the right lymphatic duct drain into?
Right subclavian vein
What does the thoracic duct drain into?
Left subclavian vein
What afferents does the upper/superior deep cervical nodes receive?
- Superficial lymph node groups
- Deeper structures tongue & tonsil (nasal cavity, nasopharynx, palate, oesophagus)
What enlarges during tonsillitis?
Jugulodigastric node (tonsillar node)
What afferents does the lower/inferior deep cervical nodes receive?
- Back of scalp & neck
- Superficial pectoral region/part of arm
- Tongue
- Superficial deep cervical glands
What drains the lymph from anterior 2/3 tongue?
Juguloomohyoid node
What does the upper & lower deep cervical nodes pass their lymph into?
Lower deep nodes & jugular trunk
What afferents does the submental nodes receive?
- Floor of mouth beneath tongue tip
- Incisor & gum
- Central lower lip
- Chin skin
Where does the Submental nodes pass lymph into?
Submandibular nodes (juguloomohyoid nodes)
What afferents does the Buccal nodes receive?
- Lower eyelid
- Cheek buccinator
- Facial vein
Where does the Buccal nodes pass lymph into?
Submandibular nodes
What afferents does the Submandibular nodes receive?
- Nose, cheek, lower lip, frontal/max/ethmoidal sinuses
- Upper/lower teeth (except lower incisor)
- Ant 2/3 tongue (except tip/centre)
- Floor of mouth
- Vestibule gums
Where does the Submandibular nodes pass lymph into?
Deep cervical nodes
What afferents does the Parotid nodes receive?
- Eyelid
- Nose
- External acoustic meatus
- Tympanic cavity
- Parts of nasal pharynx
Where does the Parotid nodes pass lymph into?
Superior deep cervical nodes
What afferents does the Mastoid nodes (post auricular) receive?
- Strip of scalp above auricle
- Posterior external auditory meatus
Where does the Mastoid nodes pass lymph into?
Superior deep cervical nodes
What afferents does the Occipital nodes receive?
Back of the scalp
Where does the Occipital nodes pass lymph into?
Deep cervical nodes
What afferents does the Superficial cervical nodes receive?
- Skin over jaw angle
- Parotid apex
- Lobule of ear
Where does the superficial cervical nodes pass lymph into?
Deep cervical nodes
What afferents does the retropharyngeal nodes receive?
- Pharynx
- Auditory tube
- Soft palate
- Hard palate
- Nose (cavities)
What afferents does the paratracheal nodes receive?
- Neighbouring structures
- Thyroid
What is the 1st node in drainage of the nasopharynx?
Node of Rouviere
What is the Pretracheal lymph node on the cricothyroid membrane also known as?
Delphian (enlarged in thyroid cancer, poor prognosis)
What is the clinical significance of tongue lymph drainage?
Lesions can spread to both sides because there is significant drainage to both sides
What makes up 90% of all oral cancers?
Squamous cell carcinoma
floor of mouth & tongue
Describe the prognosis of Squamous cell carcinoma
floor of mouth & tongue?
- Depends on whether detectable metastasis in cervical lymph nodes
- Contralateral lymph node metastasis has poor prognosis
Tumours in floor of mouth & tongue base have a higher frequency of contralateral metastasis compared to what?
Tumours in tongue tip or oropharynx
What is Troiser’s sign?
Enlarged hard (usually) left supraclavicular node (Virchow’s node)
What can an enlarged Virchow’s node indicate?
Tumour in the abdomen (esp. stomach)
Describe the structure & function of tonsils?
- Lymphoid nodules
- Increases contact with ingested organisms
- Increases exposure, destruction & facilitates development immunity
What is the Waldeye’s tonsillar ring?
Interrupted circle of protective lymph tissue (Lingual, Palatine & Pharyngeal tonsils) in upper end of alimentary respiratory tract
How do you identify & biopsy a sentinel node (pathological)?
- Identify: imaging
- Test: Histopathology
What 3 ways can you label draining lymph nodes?
- Dye marker (isosulfan blue)
- Lymphosyntigraphy (colloidal sulphur radioactive)
- Fluorescence marker (iodocyanine green near infrared imaging)
What is the preferred way to label draining lymph nodes?
Combined imaging or lymphosyntigraphy alone
Describe the treatment/management process for tumours in the head & neck when there is no node metastasis shown on examination?
- Imaging: identify sentinel node
- 2nd order & lower tier lymph nodes not examined
- Sentinel node removed & examined
- Tumour state used as guide to further treatment/prognosis (false negatives rare, can spare patient more extensive node removal)
What is increasingly recognised as a means of tumour spread in the head & neck?
Perineural spread
What are important neural routes for tumour spread in head & neck?
Trigeminal, facial & hypoglossal nerves
What is a crossroad for perineural & perivascular spread in head & neck tumours?
Pterygopalatine fossa
“communication” to orbit, oral cavity, nasal cavity, middle cranial fossa
How does the interstitial fluid get out of the brain?
Lymphatics run along the dural sinus –> deep cervical nodes
How can you tell your adequately imaging cervical spine on radiology?
Ensure you can see occiput to T1
Describe the alignment of the cervical spine?
- Lordotic curve for shock absorption
1. Posterior tip of spinous processes
2. Lamina junctional line
3. Posterior vertebral bodies
4. Anterior vertebral bodies
What 2 factors results in the lordotic alignment of the cervical spine?
- Static factors- bone shape, disc shape
2. Dynamic factors- muscle, ligament
What cervical spine bones are described as being “atypical”?
C1- Atlas
C2- Axis (dens)
C7
Describe the cartilage & joints of the intervertebral disc of cervical spine?
- Secondary cartilaginous joints
- Hyaline cartilage
- Disc is fibrous cartilage
What 3 cervical spine joints do movements occur at?
- C0-C1
- C1-C2
- C3-C7
What are the 3 ligaments in C0-C2?
- Cruciform
- Apical & ala ligamnets
- Membrana tectoria
What are the 6 ligaments in the vertebral column?
- Ligamentum nuchae
- Posterior longitudinal ligament
- Interspinous Ligament
- Supraspinous ligament
- Anterior longitudinal ligament
- Intervertebral disc
What are the 4 muscles & fascia of the neck?
- Paravertebral muscles
- Erector spinae muscles
- Pre-vertebra muscles
- Paravertebral fascia
What is the purpose & extent of the pre-vertebral fascia?
- Allows gliding
- Extends down to T3
- Covers, Floor of the posterior triangle, Cervical & brachial plexus, 3rd pt subclavian artery
Where do the vertebral vessels enter?
Foramen transversarium (C7- vein, C6- artery)
Describe the spinal injury epidemiology?
- 80% male
- 45% cervical, 25% thoracic
- 50% RTA, 30% fall, 20% sports
A person doesn’t need a cervical spine x-ray when alert & stable and…?
- <65 years
- Not serious mechanism of injury
- No tingling/sensory symptoms
- Was involved in rear-end shunt
- Sitting up
- Ambulatory since injury
- Delayed neck pain
- No cervical midline tenderness
- Able to rotate head 45 degrees either way
What are 5 dangerous mechanisms of spine injury?
- Fall >1m or 5 stairs
- Axial load to head (eg diving)
- RTA at high speed (>100km/hr), rollover or
ejection - Bicycle accidents
- Other motorised vehicle accidents
What are the 4 main mechanisms of cervical spine injury?
- Flexion
- Extension
- Compression
- Combination
What is the distance between the anterior margin of the odontoid peg & posterior aspect of C1 arch?
3mm
Describe cervical flexion injuries?
- Severe kyphosis
- “Teardrop” fragments
- Anterolisthesis
- Disrupted posterior vertebral body line
- Wide interlaminar (interspinous) space
- Narrow disc space above involved vertebra
Describe cerival compression injuries?
- Severe compressive force that explodes vertebra
- Disruption of posterior body line
- Widening of interpedicular distance
Describe cervical extension injuries?
- Wide disc space below involved vertebra
- Triangular avulsion fracture inferiorly
- Retrolisthesis
- Neural arch &/or pillar fracture
What are the 5 steps of management of spinal injury?
- Airway & Breathing, get help
- Stabilise spine, esp. neck
- Hard collar
- Log roll to get onto spinal board
- Immobilisation key to preventing worsening
What % of the population does epilepsy affect?
0.5%
What is Epilepsy?
Continuing tendency to have seizures (sudden discharged of abnormal electrical activity)
What 3 investigations would you do to diagnose epilepsy?
- ECG
- EEG
- MRI
What are the different types of Epileptic seizures?
Generalised, Primary pr Secondary (partial, simple or complex)
Describe a simple partial seizure?
- Focal with minimal spread of abnormal discharge
- Normal consciousness & awareness
Describe a complex partial seizure?
- Local onset, then spreads
- Impaired consciousness
- Manifestations vary with site of origin & degree of spread (Presence & nature of aura, Automatisms, Other motor activity)
Where is the most common site for a complex partial seizure?
Temporal lobe
Describe a Secondarily generalised seizure?
- Begin focally, with/ without symptoms
- Variable symmetry, intensity & duration of tonic (stiffening) & clonic (jerking) phases
- 1-2 minutes
- Postictal confusion & somnolence
Where is the most common site for generalised seizures?
Both hemispheres widely involved from onset
What % of generalised seizures are present in all epileptic syndromes?
40%
Describe a generalised absence seizure (Petit mal)?
- Sudden onset & abrupt cessation
- Consciousness altered
- Associated with mild clonic jerking of eyelids/extremities
- Postural tone changes
- Autonomic phenomena & automatisms
- 2.5-3.5 Hz spike & wave pattern
Describe a generalised myoclonic seizure?
Myoclonic jerking seen in wide variety of seizures, but when its the major seizure type its treated differently to from partial leading to generalized
Describe generalised atonic seizures?
- Sudden loss of postural tone
- Often in children but may be seen in adults
Describe generalised Tonic-clonic seizures (grand mal)?
- Major convulsions with rigidity (tonic) & jerking (clonic)
- Slows over 60-120s followed by stuporous state (post-ictal depression)
Describe the 2 phases of Tonic-Clonic seizures?
1) Tonic phase- muscles suddenly tense up, causing fall to the ground if they are standing
2) Clonic phase- muscles will contract
& relax rapidly, causing convulsions
What are the 2 non-convulsive seizures?
- Atonic seizures
2. Absence seizures
Describe status epilepticus?
- More than 30mins of continuous seizure
- 2+ sequential seizures spanning this period without full recovery between seizures
- Medical emergency
Describe the current pharmacotherapy for epileptic patients?
- <60% become seizure free with drug therapy
- Another 20% seizures can be drastically reduced
- ~20% epileptic patients, seizures are refractory to currently available AEDs
What 7 factors help you chose which anti-epileptic drug to prescribe?
- Seizure type
- Epilepsy syndrome
- Pharmacokinetic profile
- Interactions/medical conditions
- Efficacy
- Expected adverse effects
- Cost
What are the 5 targets for antiepileptic drugs?
- Increase inhibitory neurotransmitter system (GABA)
- Decrease excitatory neurotransmitter system (glutamate)
- Block voltage-gated inward positive currents( Na+ or Ca++)
- Increase outward positive current (K+)
- Many AEDs pleiotropic (multiple mechanisms)
Describe the 2 groups of glutamate receptors?
- Ionotropic (fast)
2. Metabotropic (slow)- Regulation of second messengers (cAMP & Inositol), Modulation of synaptic activity
What 4 things can modulate glutamate receptors?
- Glycine
- Polyamine sites
- Zinc
- Redox site
Give 4 examples of antiepileptic drugs which act primarily on Na+ channels?
- Phenytoin, Carbamazepine
- Oxcarbazepine
- Zonisamide
- Lamotrigine
How does Phenytoin & Carbamazepine work in epilepsy treatment?
Block voltage dependent sodium channels at high firing frequencies
How does Oxcarbazepine work in epilepsy treatment?
Blocks voltage-dependent sodium channels at high firing frequencies & also effects K+ channels
How does Zonisamide work in epilepsy treatment?
Blocks voltage-dependent sodium channels & T-type calcium channel
What are the 6 commonly used major antiepileptic drugs?
- Lamotrigine
- Sodium Valproate
- Carbamazepine
- Oxcarbazepine
- Levetiracetam
- Topiramate
Describe Lamotrigine to treat epilepsy?
- Inhibiting sodium channels
- Broad therapeutic profile
- Side-effects: hypersensitivity reactions (especially skin rashes)
Describe Sodium Valproate to treat epilepsy?
- Chemically unrelated to other antiepileptics
- Causes increase in GABA content of the brain
- Weak inhibition of GABA transaminase
- Effect Na channels
- Side effects: hair loss, teratogenicity & foetal syndrome, liver damage
Describe Carbamazeprine to treat epilepsy?
- Derivative of tricyclic antidepressants
- Good for partial seizures & trigeminal neuralgia
- Strong enzyme-inducing agent
- Side effect: sedation, ataxia, mental disturbances, water retention
What may Carbamazeprine exacerbate?
Primary generalised seizures
Describe Oxcarbazepine to treat epilepsy?
- May augment K+ channels
- Some induction of P450
- Sedating but less toxic than Carbamazapine
Describe Levetiracetam to treat epilepsy?
- Probably inhibits presynaptic Ca
- Analogue of piracetam
- Useful in partial seizures & generalised seizures
- Psychiatric side effects
Describe Topiramate to treat epilepsy?
- Risk of teratogenesis
- Low titration to avoid cognitive side effects
Describe Tiagabine to treat epilepsy?
- GABA-uptake inhibitor
- Side-effect: dizziness & confusion
- Licensed for partial seizures
Describe Zonisamide to treat epilepsy?
- Blocks Na channels
- Can cause anorexia & somnolence
Describe Phenytoin (old drug) to treat epilepsy?
- Saturation kinetics, therefore, plasma concentration can vary widely & monitoring needed
– Side effect: confusion, gum hyperplasia, skinrashes,
anaemia, teratogenesis, cerebellar syndrome, osteoporosis
What is Phenytoin also used as?
Antidysrhythmic agent
What is Phenytoin not effective for?
Absence seizures
Describe Ethosuximide (old drug) to treat epilepsy?
- Treat absence seizures in children
- Blocks T-type calcium channels
- Side effect: nausea & anorexia
Describe Phenobarbitone (old drug) to treat epilepsy?
- Enzyme inducing, very long half-life
- Osteoporosis
What are the 2 benzodiazepines used as 1st line treatment for status epilepticus?
Lorazapam & Diazepam (IV)
What is Gabapentin & its 2nd generation derivative Pregabalin used in?
- Add-on therapy for partial seizures & tonic-clonic seizures
- Main uses in Neuropathic pain
What is the treatment for epileptic children?
- Valproate 1st line
- Lamotrigine, Levetiracetam increasingly being used
- Ethosuxamide for Primary generalised
What is the treatment for status epilepticus?
- Diazepam, lorazapam IV (fast, short acting)
- Then phenytoin, fosphenytoin, or phenobarbital (longer acting) when control is established
Describe when you would use neurosurgery for epilepsy?
- Common for partial seizures
- Tried atleast 3 antiepileptic drugs
- Work-up includes detailed electrophysiology
- Ideally non-dominant hemisphere
When do you get the best result for neurosurgery in epilepsy?
When lesion correlates with EEG
Describe the mode of action of Baclofen drug?
- Agonist on GABA B-receptors
- Action exerted mainly at level of spinal
cord to inhibit motoneurons
What is Baclofen drug used for?
- Effective orally &for treatment of spasticity associated with multiple sclerosis or spinal injury.
- Ineffective for cerebral spasticity caused by birth injury & epilepsy
Describe the cartilage & joint of the vertebral facet joint?
- Synovial joint
- Hyaline cartilage
- Enables movement
